Abstract
High-sensitivity mass spectrometry assays are available to detect monoclonal immunoglobulins. To better assess the prevalence of monoclonal gammopathy of undetermined significance (MGUS), we identified 300 patients diagnosed with MGUS or related gammopathy who had a prior negative work-up for monoclonal proteins as part of the Olmsted County MGUS screening study. Two mass spectrometry-based detection methods (matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) and monoclonal immunoglobulin rapid accurate mass measurements (miRAMM) along with traditional immunofixation were performed on the Olmsted baseline and MGUS diagnostics serum samples. Among the 226 patients considered negative for MGUS based on protein electrophoresis and serum-free light-chain assay, a monoclonal protein could be detected at baseline in 24 patients (10.6%) by immunofixation, 113 patients (50%) by MADLI-TOF mass spectrometry, and 149 patients (65.9%) by miRAMM mass spectrometry. In addition, using miRAMM, some patients demonstrated an oligoclonal to monoclonal transition giving insight into the origin of MGUS. Using the sensitive miRAMM, MGUS is present in 887 of 17,367 persons from the Olmsted County cohort, translating into a prevalence of 5.1% among persons 50 years of age and older. This represents the most accurate prevalence estimate of MGUS thus far.
Highlights
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder that is present in ~3–4% of the general population over the age of 501–3
Previous mathematical estimates suggest that when MGUS is first clinically recognized, it has likely been present in an undetected state for a median duration of >10 years[7]
Screening cohort who were negative for MGUS or lightchain MGUS during the initial screening period, monoclonal gammopathy was clinically diagnosed during subsequent follow-up in 300 patients
Summary
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder that is present in ~3–4% of the general population over the age of 501–3. Previous mathematical estimates suggest that when MGUS is first clinically recognized, it has likely been present in an undetected state for a median duration of >10 years[7]. To verify these estimates, a serum-based method with higher analytical sensitivity than SPEP is needed.
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